CHEM243H

P. T. GUNNING

CHEM243H ORGANIC CHEMISTRY

P. T. GUNNING

The chemistry of carbon-based compounds: hydrocarbons and their derivatives How carbon bonds to itself or different atoms such as oxygen, nitrogen, sulfur and/or halogens to form different molecules How these molecules interact with the environment that they are in
O OH O O Cl O Cocaine H3C H O N O O H3C N O O O O Crack Cocaine (free base) Juicy Fruit HO O O

Organic Chemistry CHM243H5F 2012

Prof. Patrick T. Gunning Rm 4046

Acetylsalicylic Acid (ASA or Aspirin)

Prof Gunning = (01/2012)

Do some cool chemistry = (illegally, see above)

CHEM243H

P. T. GUNNING

CHEM243H Why Study Organic Chemistry?

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Extraction
OH O HO OH O Vanillin -D-glucoside
O HO O H Vanillin

O O HN N O S O N N N N

Synthetic
Viagra is a synthetic molecule designed specifically to fit into an enzyme and complete with the naturally produced molecule: cGMP
O HN H2N N N N O O O P OH O OH

O O H OH

One of the most dynamic and exciting fields of scientific research, involved in . - Medicinal Chemistry - drug discovery (that is what I do!) - Materials and Polymers - plastics - Petrochemical Industry - Explosives Industry - weapons, ejector seats. - Its better than Physics - Its much better than biology!
O S O N N O HN N O N N

Viagra

Billion Dollar Industries $$$ Being a chemist is cool! A chemist gets to design and synthesize molecules - we can manipulate atoms! We can alter Natures molecules to do new and wonderful things Organic chemistry is difficult but can be learned with hard work and with practice PRACTICE, PRACTICE, PRACTICE!
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Vanilla is the only edible fruit in the orchid family. Synthetic vanilla contains only one organic component vanillin. Vanilla contains so many other flavors and fragrance components, it has a much richer smell and taste than vanillin does by itself.

cGMP

- Viagra potently inhibits the enzyme PDE-5, which destroys cyclic guanosine monophosphate (cGMP), itself a dilator of blood vessels in the body. - Viagra allows cGMP to persist and led to its use for oral treatment of male erectile disfunction.
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CHEM243H Synopsis of Course Objectives

P. T. GUNNING

CHEM243H CHEM243 - EXAMS Marking Scheme: Laboratory - 20 % -

P. T. GUNNING

The chemistry of benzene, alcohols, aldehydes, ketones, carboxylic acid, esters, acid chlorides, amides and amines will be covered. As well, electrophilic aromatic substitution, protection and deprotection of alcohols, nucleophilic acyl substitution, nucleophilic addition, carbonyl alpha-substitution reaction, ketoenol tautomerism, carbonyl ccondensation and proton NMR will be introduced. The emphasis will be on organic mechanisms and application of organic reactions to multistep synthesis WE WILL COVER A LOT OF MATERIAL! Organic chemistry is a language you need to practice in order to improve and to keep on top of the increasing number of material, terminology, reactions..etc You MUST come to class!

Mid-term test # 1 - 15 % Mid-term test # 2 - 15 % Final exam - 50 %

Wednesday, February 29th, 2012, 11:10 - 12:00 Wednesday, March 21st, 2012, 11.10 12.00 TBA

If you miss the test and cannot provide a medical note, you will get zero for that test. For the final exam you will be responsible for all the material covered in the course beginning in September. Mid-Term Test Dates: Wednesday, Feb. 29th, 2012, 11:10 - 12:00. (For that test you will be responsible for all the work covered up to Monday, 27th Feb.) Wednesday, Mar 21st, 2012, 11:10 12.00. (For that test you will be responsible for all the work covered up to Monday, 19th Mar) There will be no make-up term tests in this course. If you miss this the class test due to a medical reason accompanied by a doctors note, the final exam will be worth 65% of your final mark. 6

CHEM243H Course Textbook

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CHEM243H Course Syllabus - Brief overview

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Chapter 15: Benzene and aromaticity

Organic Chemistry John McMurry

Chapter 16: Chemistry of benzene: electrophilic aromatic substitution Start Wed Chapter 17: Alcohols and phenols Chapter 19: Aldehydes and ketones: nucleophilic addition reactions Chapter 20: Carboxylic acids and nitriles Chapter 21: Carboxylic acid derivatives - nucleophilic acyl substitution reactions Chapter 22: Carbonyl alpha - substitution reactions Chapter 23: Carbonyl condensation reactions Chapter 24: Amines and Heterocycles
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The course work that presented will follow the text book faithfully McMurry is an extremely easy to read text book - and you should do so regularly! Practicing problems is the best way to improve your knowledge.

CHEM243H Lecturing style

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CHEM243H OFFICE HOURS: 4046 William G Davis Building Monday Wednesday Friday 2:00 3:45 2:00 3:45 2:00 3:45

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I will provide lecturing handouts to every student on blackboard the night before lecture or earlier You will be expected to fill in the blanks provided with chemical structures and reaction mechanisms I want you to spend more time drawing curly arrow mechanisms rather than writing about the reactions! I will be examining you on your ability to draw mechanisms and on your understanding of how reactions work, so it is important that you get as much practice as possible

If I am not in my office I will be in my laboratory 3023C. EMAIL/PHONE CALL POLICY - PLEASE DONT EMAIL ME! - Im not good at replying (and cant guarantee I will!) - I dont reply to my girl friend I probably wont reply to you - If you have a problem/emergency, come and see me in person

Dont feel intimidated, I am friendly and approachable - I will do all I can to help you!

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CHEM243H FINAL EXAM 3-hour final exam Held during the Spring examination period

P. T. GUNNING

CHEM243H At a minimum what you need to know from the first term, CHM 242! sp3, sp2, sp hybridization for C, N, O

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Understand concept of Lewis base and acid, nucleophiles and electrophiles Simple nomenclature Stereochemistry R, S, cis, trans, E, Z how to recognize them and know how to draw them How to write detailed mechanisms and how to make proper use of arrows for writing mechanisms. (This is extremely important) How to calculate degrees of unsaturation helpful with NMR problem(s) Understand why and which double bonds are more stable Understand the differences in stability between 1, 2, 3 carbocations and radicals Understand the importance of resonance structures. Know how to recognize resonance structures and how to draw them Know the difference between inductive and resonance effects Understand Markovnikov and Zaitsev rules Recognize similarities between allylic and benzylic substituted compounds

Students will be responsible for all work covered in the course even labs Mid-term test and final exam: questions will be problem solving and testing understanding as opposed to essay questions YOU ARE NOT IN BIOLOGY ANYMORE! Memorization will not get you an A, B or even C mark in this class! No extra marks will be given to any student after the term is over. The mark you receive will be the mark you have earned in the course.

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CHEM243H Functional Groups - Learn this asap!

Amine Aldehyde Ketone Carboxylic acid Ester Amide

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CHEM243H ELECTRONEGATIVITY

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Nitrile

- Understanding electronegativity is the first step to understanding organic rxns and bonding

O
H

O OH

O O

O N H
O

Measure of tendency for an atom in a molecule to attract a C N

RCN

The greater the no. of protons the greater the nuclear charge

RNH2 R2NH R 3N

O RCH

O RCR'

O RCOH

RCNH2
O RCOR'
O RCNHR' O
RCNR'R"

increases CH3NH2

CH3NH2

O CH3CH
Ethanal Acetaldehyde

O CH3CCH3
Propanone Acetone

O CH3COH

O CH3COCH3

O CH3CNH2

Electronegativity
increases

Methanamine Methylamine

Ethanoic acid Acetic acid

Methyl ethanoate Methyl acetate

Ethanamide Acetamide

Ethanenitrile Acetonitrile 13

Attraction between oppositely charged particles increases with decreasing distance

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CHEM243H ELECTRONEGATIVITIES OF COMMON ELEMENTS

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CHEM243H BOND TYPE Difference in electronegativity (EN)

NONPOLAR COVALENT

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POLAR COVALENT

- derived from gas phase bond dissociation energies the amount of energy released when a bond forms (-ve value) or the amount of energy needed to break a bond (+ve value) - Fluorine is the most electronegative (electronegativity of - ) - Lithium is the least electronegative (electronegativity of - )

Cl

Cl

C
+

O C O

Cl
COVALENT BONDS

Cl

0 to 0.4

0.5 to 1.6

- Covalent bonds occur between atoms of similar electronegativity (close together in table) - Atoms achieve octets by sharing of valence electrons - Molecules result from this covalent bonding - Valence electrons can be indicated by dots (electron-dot formula or Lewis structures) Two electrons in a bond are indicated by a line (one line = two electrons)
H2 H + H H H OR H
H HC H H

H
H

How does this relate to bonding?

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CH4

OR

C H

H
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CHEM243H POLAR COVALENT BONDS - The sharing of electrons unequally due to differences in electronegativity - Results in atoms having a partial negative (-) or partial positive charge (+)

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CHEM243H WRITING LEWIS STRUCTURES: - Atoms bond using their valence electrons - The number of valence electrons is equal to the group number of the atom - Carbon is in Group 4 and has 4 valence electrons

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If a molecule has a ve charge like a hydroxide anion, where would it attack chloromethane?

- Hydrogen is in Group 1 and has 1 valence electron - Oxygen is in group 6 and has 6 valence electrons - Nitrogen is in group 5 and has 5 valence electrons - To construct molecules the atoms are assembled with the correct number of valence electrons - The structure is written to satisfy the octet rule for each atom and to give the correct charge

- Electron density is pulled towards the oxygen atom, why? -

If necessary, multiple bonds can be used to satisfy the octet rule for each atom Draw the Lewis Structure for CO2 C 4 valence es O 2 x 6 valence es TOTAL = Each atom must have 8 es

es

Draw the Lewis Structure for CN17 18

CHEM243H FORMAL CHARGES

P. T. GUNNING

CHEM243H

P. T. GUNNING

- created by an imbalance in the no. of protons in the nucleus and es surrounding the nucleus Ammonia NH3 electronic configuration of N = 1s22s22p3 5 valence electrons

PRACTISE: WHAT IS THE FORMAL CHARGE ON THE FOLLOWING MOLECULES? Which atom bears the charge?
CH3OH CH3O
N

CH3OH2

What is the formal charge on Nitrogen?

Total number of electrons = Total number of protons Charge on N atom = =

How many lone pairs of electrons are around the oxygen atom? What is the charge on the carbon atom? There are no lone pairs on the carbon.
CH3 CH3

Ammonium, NH4 charged? Total number of electrons = Total number of protons Charge on N atom = =

N should be = 1s22s22p3

1s22s22p2 What is the formal charge on the sulfur atom? (all atoms have full octets)
S

H3C

What is the formal charge on the nitrogen atom? (all atoms have full octets)
O N O

Nitrogen should have 5 valence electrons but only has 4. Since it has one more proton than electron surrounding the nucleus of the nitrogen atom, it is positively charged

What is the charge on the carbon atom?

H3C

CH2

What is the charge on the oxygen atoms?

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CHEM243H RESONANCE

P. T. GUNNING

CHEM243H RULES FOR RESONANCE 1) 2) 3)

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As seen in different examples, you may be able to draw molecules in which there are different combinations of bonding. Which is the correct structure of the carbonate ion (CO32-)?
O O O

4) - Experimentally, in carbonate, all bonds are of equal length and the charge is spread equally over all three oxygen atoms. The real structure is a resonance hybrid or a mixture of all three resonance structures - One resonance contributor is converted to another by the use of curly arrows which show the flow of electron density in a resonance structure - In reaction mechanisms, the arrows will show us the movement of electrons between molecules - The use of arrows serves as an electron bookkeeping device and to help us think about where the electrons can possibly flow -
H

All structures must be proper Lewis structures

O H C H H O H N H H O Carbon has 5 bonds!!

- You cannot exceed the octet rule for elements in rows 1 and 2 - The overall charge of each resonance structure MUST stay the SAME!!

H C H H O H N H

Nitrogen has 4 bonds and 1 lone pair of electrons 10 electrons around the nitrogen

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CHEM243H RESONANCE STABILIZATION

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CHEM243H BOND OVERLAP and RESONANCE

1.54 H3C CH3 , (sp - sp) 1.20 HC CH , (sp - sp), (p-p)
o o o o

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o

- The energy of the molecule as a whole is lower than the energy of any single contributing resonance form this lowering of energy is called -- Equivalent resonance forms make equal contributions to the structure of the real molecule Structures with equiv. resonance forms tend to be greatly stabilized: the more equiv. resonance structures a molecule has, the more stable it is - The most important resonance contributors are structures with - When charges exist, the structure with the least amount of charges is favoured (i.e. 1 +ve charge vs 2 +ve charges and 1 ve charge) - When structures have the same no. of charges, the structure with least amount of charge separation of opposite charges are favoured - Also, charges are preferably on atoms with compatible electronegativity

1.34 H2C CH2 , (sp2 - sp2), (p-p) 1.46 HC C CH3 , (sp - sp3)
o

1.50 H2C C CH3 H , (sp2 - sp3) 1.43 HC C C CH2 H , (sp - sp2)

o

1.47 H2C C C CH2 H H , (sp2 - sp2) 1.37 HC C C CH , (sp - sp)

o

Why does the bond length between the carbon-carbon single bonds become smaller as the hybridization changes from sp3 to sp? Because the sp3 orbitals have more p character and are longer. The more s character the orbital has the smaller and shorter it is. [sp3 (1/4 s, 3/4 p), sp2 (1/3 s, 2/3 p), sp (1/2 s, 1/2 p)] Conjugation: systems that have a p-orbital on an atom adjacent to a double bond; Conjugated unsaturated systems have delocalized bonds
saturated

A) No charges on it therefore it is a major contributor B) Opposite charges have minimal separation and compatible electronegativity C) Opposite charges have more separation and positive charge less favourable on an oxygen 23 versus a carbon (based on electronegativity)

unsaturated conjugated & unsaturated

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CHEM243H
Hydrogenation H2/Ni H = -30.3 kcal/mol

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CHEM243H BOND OVERLAP and RESONANCE Conclusion: Two conjugated bonds are connected.

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WHAT EFFECT DOES CONJUGATION HAVE ON THE STABILITY OF A MOLECULE?

HOW? There is some overlap of adjacent electrons which shortens the C2-C3 bond and helps stabilize the molecule. What is causing the overlap of adjacent electrons? Examine the various resonance forms:

H2/Ni

H = -60.6 kcal/mol WE WOULD ASSUME THAT H = 2 x -30.3 kcal/mol = -60.6 kcal/mol OBSERVED H = -57.1 kcal/mol

H2/Ni

For an exothermic reaction the more heat given off the less stable the molecule is
Potential Energy
MORE STABLE THAN CALCULATED H = -60.6 kcal/mol H = -57.1 kcal/mol

Reaction Coordinate

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The major resonance contributor shows alternating single and double bonds, however, the three other resonance structures illustrate a double between C2 and C3. Since these three resonance structures are all minor contributors, the molecule will illustrate double bond character between C2 and C3. 26

CHEM243H RESONANCE

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CHEM243H RESONANCE Draw resonance structures for the following anion:

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Remember: only lone pairs of electrons, double bonds or triplebonds can resonate!
H H H H H H

H H H

H H

- The resonance arrow starts at the C atom that has the lone pair of electrons and negative charge. The arrow ends between the two C atoms to show the formation of a new bond - The blue arrow is needed because you cant have 5 bonds on a carbon atom. The arrow starts between the C atoms (the bond) and ends on the terminal C.

H H H

H H

The use of a double headed arrow shows the movement of two electrons (an electron pair) Resonates to be more stable the charge is spread to stablize the whole molecule27
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CHEM243H

P. T. GUNNING

CHEM243H Structure and Stability of Benzene: Molecular Orbital Theory Benzene is unsaturated Benzene doesnt undergo usual alkene reactions
Br2 Fe catalyst H Br
+ Br2 Fe catalyst Bromobenzene Br + HBr

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NOW LETS LOOK AT THE STABILITY OF BENZENE, A CONJUGATED RING SYSTEM Benzene is much more stable than would be expected based on calculations for cyclohexatriene Theoretical: 3 x hydrogenation of cyclohexene + 3 x double bond stabilization (3 x 120) + (3 x 10) = -330 kJ/mol Observed: Difference = WHY? -Correct Incorrect

Br

Br

Br H (Addition product not formed)

Electron density maps show that electron density in all six C-C bonds is identical Benzene is a planar molecule - shaped like a regular hexagon C-C-C bonds are 120 All Cs are sp2 hybridized - each C has a p-orbital perpendicular to the plane of the 6- ring Each C is equivalent impossible to define 3 localized bonds in which a given p orbital overlaps with only one neighbouring p orbital Kekul Benzene is an aromatic compound a most important structure in organic chemistry Almost all drugs contain aromatic structures.
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Each p-orbital overlaps equally well with both neighbouring p orbitals The 6 electrons are completely delocalized around the ring!

CHEM243H WHAT MAKES A MONOCYCLIC COMPOUND AROMATIC? - Aromaticity and the Huckel 4n + 2 Rule The structure must be --

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CHEM243H Is there an easier way of determining the MOs?

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Polygon rule: The energy level diagrams for the molecular orbitals resulting from a combination of any cyclic arrangement of p orbitals can be deduced from the appropriate sided polygon. MO energy diagram of a completely conjugated cyclic system has the same shape as the compound with one vertex (the all bonding) at the bottom

Each atom in the ring must have an unhybridized p-orbital (usually sp2 or sp hybridized) The unhybridized p orbitals must overlap to form a continuous ring of parallel orbitals The structure must be planar or nearly planar Delocalization of the electrons over the ring must lower the electronic energy Cyclobutadiene
4 electrons in 4 atomic orbitals, when combined will form 4 molecular orbitals Both degenerate MOs have 2 bonding and 2 antibonding for a net bonding order of zero
TWO NODES

4*

ANTI-BONDING ORBITAL

The energies of the MOs will be where the corners touch the circle Lets look at benzene and cyclooctatetrane again 2 non-bonding orbitals each with 1 electron - This is an unstable configuration; adopts a non-planar with localized p orbitals to avoid instability

Nodal plane

Nodal plane

NON-BONDING ORBITAL

No nodes

BONDING ORBITAL

Cyclobutadiene is not aromatic and is very reactive and unstable If electrons were delocalized it would be a diradical (two unpaired electrons)
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CHEM243H WHAT DOES IT MEAN: A COMPOUND IS AROMATIC? Aromatic Compounds Aromatic compounds are more stable than their open-chained counterparts

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CHEM243H SUMMARY OF AROMATICITY Huckels Rule

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Delocalization of the electrons makes it more stable, less reactive (than predicted) Anti-aromatic Compounds Antiaromatic compounds have continuous p orbitals but delocalization of the electrons increases the electron energy (less stable). Thus, are destabilized by conjugation Numeric Patterns and Aromaticity

Planar monocyclic rings with a continuous system of p-orbitals and 4n + 2 electrons are aromatic (n = 0, 1, 2, 3 etc) - Aromatic compounds have substantial resonance stabilization - Benzene is aromatic: it is planar, cyclic, has a p-orbital at every carbon, and 6 electrons (n =1) There is a polygon-and-circle method for deriving the relative energies of orbitals of a system with cyclic continuous array of p orbitals - A polygon corresponding to the ring is inscribed in a circle with one point of the polygon pointing directly down

4 electrons 4n n=1

6 electrons 4n + 2 n=1

8 electrons 4n n=2

10 electrons 4n + 2 n=2

12 electrons 4n n=3

14 electrons 4n + 2 n=4

- A horizontal line is drawn where vertices of the polygon touch the circle - Each line corresponds to the energy level of the MOs at those atoms - A dashed horizontal line half way up the circle indicates the separation of bonding and antibonding orbitals Benzene has 3 bonding and 3 antibonding orbitals - All the bonding orbitals are full and there are no electrons in the antibonding orbitals; benzene has a closed shell of delocalized electrons and is very stable

Huckels Rule: To be aromatic, all atoms must have an unhybridized p orbital, conjugated, planar and have 4n + 2 electrons, where n is an integer (n = 0, 1, 2, 3,.) Therefore, molecules with - Molecules with 4n electrons are said to be - Even if planar and conjugated!! - Delocalization of their electrons would lead to their 33 destabilization

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